Kim DH

References (55)

Title : The impact of depression on language function in individuals with Alzheimer's disease: a pre\/post-treatment design - Yoon_2023_Ann.Gen.Psychiatry_22_4
Author(s) : Yoon KH , Moon YS , Kim DH
Ref : Ann Gen Psychiatry , 22 :4 , 2023
Abstract : BACKGROUND: It is uncertain whether depression might affect cognitive function in Alzheimer's disease (AD). Most of studies on the effect of depression treatment on cognitive function in AD were briefly evaluated by Mini-Mental State Examination (MMSE). MMSE is poor sensitive to detect cognitive change. This study examined the cognitive response to depression treatment in AD via multi-domain assessment. In addition, we explored whether effect of depression treatment in AD is different those of late-life depression (LLD). METHODS: This study include AD patients with depression (AD + D) and without depression (AD - D), LLD patients (LLD), and healthy controls (HC). The patients were treated according to their diagnosis for 16 weeks: acetylcholinesterase inhibitors (AChEIs) and selective serotonin reuptake inhibitors (SSRIs) for AD + D, AChEIs for AD - D, and SSRIs for LLD. The cognitive changes from pre- to post-treatment were compared between AD + D and AD - D or LLD and HC. An independent sample t test was performed to compare the degree of change between the groups. Paired t tests were used to determine cognitive function changes in each depression treatment responder group. RESULTS: At baseline, AD + D had more impairment in language function compared to AD - D, and LLD had greater deficit in executive function than HC. After depression treatment, more impaired cognitive domains at baseline were improved in AD + D and LLD, respectively. Moreover, AD + D showed an improvement in the global cognitive function (MMSE). CONCLUSIONS: Results indicated that language function was influenced by depression in AD, which is first evidence for specific cognitive domain related to depression in AD. Our finding indicates that depression could negatively impact cognitive function, and depression treatment may have beneficial cognitive effect in both AD and LLD. This study suggests the importance of early detection and treatment of depression in AD and LLD. Trial registration Clinical Research Information Service, CRIS, ID#: KCT0004041, Registered 5 June 2019, retrospectively registered after first patient enrollment date (4 March 2014) .
ESTHER : Yoon_2023_Ann.Gen.Psychiatry_22_4
PubMedSearch : Yoon_2023_Ann.Gen.Psychiatry_22_4
PubMedID: 36737766

Title : Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus - Baek_2022_Signal.Transduct.Target.Ther_7_367
Author(s) : Baek YB , Kwon HJ , Sharif M , Lim J , Lee IC , Ryu YB , Lee JI , Kim JS , Lee YS , Kim DH , Park SI , Kim DK , Choy HE , Lee S , Choi HS , Osborne TF , Jeon TI , Cho KO
Ref : Signal Transduct Target Ther , 7 :367 , 2022
Abstract : The biosynthesis of host lipids and/or lipid droplets (LDs) has been studied extensively as a putative therapeutic target in diverse viral infections. However, directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated. Here, we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids (FFAs) at the late stage of diverse RNA viral infections, which represents a broad-spectrum antiviral target. Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection, thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy. The replication of SARS-CoV-2 and influenza A virus (IAV), which is suppressed by the treatment with LD-associated lipases inhibitors, is rescued by supplementation with FFAs. The administration of lipase inhibitors, either individually or in a combination with virus-targeting drugs, protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters. Moreover, the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2- and IAV-challenged animals, a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients. In conclusion, the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19- and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.
ESTHER : Baek_2022_Signal.Transduct.Target.Ther_7_367
PubMedSearch : Baek_2022_Signal.Transduct.Target.Ther_7_367
PubMedID: 36253361

Title : DW2009 Elevates the Efficacy of Donepezil against Cognitive Impairment in Mice - Lee_2021_Nutrients_13_
Author(s) : Lee DY , Kim JK , Yun SW , Han MJ , Kim DH
Ref : Nutrients , 13 : , 2021
Abstract : Lactobacillus plantarum C29 and DW2009 (C29-fermented soybean) alleviate cognitive impairment through the modulation of the microbiota-gut-brain axis. Therefore, we examined whether combining donepezil, a well-known acetylcholinesterase inhibitor, with C29 or DW2009 could synergistically alleviate cognitive impairment in mice. Oral administration of donepezil combined with or without C29 (DC) or DW2009 (DD) alleviated lipopolysaccharide (LPS)-induced cognitive impairment-like behaviors more strongly than treatment with each one alone. Their treatments significantly suppressed the NF-kappaB(+)/Iba1(+) (activated microglia) population, NF-kappaB activation, and tumor necrosis factor-alpha and interleukin-1beta expression in the hippocampus, while the brain-derived neurotropic factor (BDNF)(+)/NeuN(+) cell population and BDNF expression increased. Their treatments strongly suppressed LPS-induced colitis. Moreover, they increased the Firmicutes population and decreased the Cyanobacteria population in gut microbiota. Of these, DD most strongly alleviated cognitive impairment, followed by DC. In conclusion, DW2009 may synergistically or additively increase the effect of donepezil against cognitive impairment and colitis by regulating NF-kappaB-mediated BDNF expression.
ESTHER : Lee_2021_Nutrients_13_
PubMedSearch : Lee_2021_Nutrients_13_
PubMedID: 34579150

Title : Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches - Hwang_2021_Nutrients_13_
Author(s) : Hwang J , Youn K , Lim G , Lee J , Kim DH , Jun M
Ref : Nutrients , 13 : , 2021
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid beta peptide (Abeta) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS.
ESTHER : Hwang_2021_Nutrients_13_
PubMedSearch : Hwang_2021_Nutrients_13_
PubMedID: 33477276

Title : Establishment of a Rapid Micropropagation System for Kaempferia parviflora Wall. Ex Baker: Phytochemical Analysis of Leaf Extracts and Evaluation of Biological Activities - Park_2021_Plants.(Basel)_10_
Author(s) : Park HY , Kim KS , Ak G , Zengin G , Cziaky Z , Jek J , Adaikalam K , Song K , Kim DH , Sivanesan I
Ref : Plants (Basel) , 10 : , 2021
Abstract : This study aimed to establish a rapid in vitro plant regeneration method from rhizome buds of Kaempferia parviflora to obtain the valuable secondary metabolites with antioxidant and enzyme inhibition properties. The disinfection effect of silver oxide nanoparticles (AgO NPs) on rhizome and effects of plant growth regulators on shoot multiplication and subsequent rooting were investigated. Surface sterilization of rhizome buds with sodium hypochlorite was insufficient to control contamination. However, immersing rhizome buds in 100 mg L(-1) AgO NPs for 60 min eliminated contamination without affecting the survival of explants. The number of shoots (12.2) produced per rhizome bud was higher in Murashige and Skoog (MS) medium containing 8 microM of 6-Benzyladenine (6-BA) and 0.5 microM of Thidiazuron (TDZ) than other treatments. The highest number of roots (24), with a mean root length of 7.8 cm and the maximum shoot length (9.8 cm), were obtained on medium MS with 2 microM of Indole-3-butyric acid (IBA). A survival rate of 98% was attained when plantlets of K. parviflora were acclimatized in a growth room. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to determine the chemical profile of K. parviflora leaf extracts. Results showed that several biologically active flavonoids reported in rhizomes were also present in leaf tissues of both in vitro cultured and ex vitro (greenhouse-grown) plantlets of K. parviflora. We found 40 and 36 compounds in in vitro cultured and ex vitro grown leaf samples, respectively. Greenhouse leaves exhibited more potent antioxidant activities than leaves from in vitro cultures. A higher acetylcholinesterase inhibitory ability was obtained for greenhouse leaves (1.07 mg/mL). However, leaves from in vitro cultures exhibited stronger butyrylcholinesterase inhibitory abilities. These results suggest that leaves of K. parviflora, as major byproducts of black ginger cultivation, could be used as valuable alternative sources for extracting bioactive compounds.
ESTHER : Park_2021_Plants.(Basel)_10_
PubMedSearch : Park_2021_Plants.(Basel)_10_
PubMedID: 33916375

Title : In Vitro Enzyme Inhibitory Properties, Secondary Metabolite Profiles and Multivariate Analysis of Five Seaweeds - Mahomoodally_2020_Mar.Drugs_18_
Author(s) : Mahomoodally MF , Bibi Sadeer N , Zengin G , Cziaky Z , Jeko J , Diuzheva A , Sinan KI , Palaniveloo K , Kim DH , Rengasamy KR
Ref : Mar Drugs , 18 : , 2020
Abstract : Seaweeds have been exploited as both food products and therapeutics to manage human ailments for centuries. This study investigated the metabolite profile of five seaweeds (Halimeda spp., Spyridia hypnoides (Bory de Saint-Vincent) Papenfuss, Valoniopsis pachynema (G. Martens) Borgesen, Gracilaria fergusonii J. Agardh and Amphiroa anceps (Lamarck) Decaisne using ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UHPLC-ESI-MS/MS). Furthermore, these seaweeds were assessed for antioxidant and inhibitory effects against alpha-amylase, alpha-glucosidase, acetyl-cholinesterase (AChE), butyryl-cholinesterase (BChE) and tyrosinase. Valoniopsis pachynema and A. anceps yielded the highest flavonoid (4.30 +/- 0.29 mg RE/g) and phenolic content (7.83 +/- 0.08 mg RE/g), respectively. Additionally, A. anceps exhibited significant antioxidant properties with all assays and significantly depressed BChE (IC50 = 6.68 +/- 0.83 mg/mL) and alpha-amylase activities (IC50 = 5.34 +/- 0.14 mg/mL). Interestingly, the five seaweeds revealed potent inhibitory effects against tyrosinase activity. In conclusion, A. anceps might be considered as a key source of phytoantioxidants and a potential candidate to develop nutritional supplements. Besides, the five tested seaweeds warrant further study and may be exploited as promising natural sources for managing hyperpigmentation.
ESTHER : Mahomoodally_2020_Mar.Drugs_18_
PubMedSearch : Mahomoodally_2020_Mar.Drugs_18_
PubMedID: 32276531

Title : Screening of Bioactive Metabolites and Biological Activities of Calli, Shoots, and Seedlings of Mertensia maritima (L.) Gray - Song_2020_Plants.(Basel)_9_
Author(s) : Song K , Sivanesan I , Ak G , Zengin G , Cziaky Z , Jek J , Rengasamy KR , Lee ON , Kim DH
Ref : Plants (Basel) , 9 : , 2020
Abstract : Mertensia maritima (L.) Gray is threatened with extinction owing to climate change, poor seed germination, and ocean warming. In vitro explant-culture is used for ex situ preservation and plantlet massive production. In vitro cell and organ cultures serve as an alternative plant material source to investigate the biological activities and phytochemical profiles of rare plants. We aimed to develop an efficient callus and shoot production protocol and investigate bioactive metabolites, antioxidants, and enzyme inhibitory potential of M. maritima calli, shoots, and in vivo seedlings. The effects of combinations of different plant growth regulators, 6-BA (N(6)-benzyladenine), 6-KN (Kinetin), TDZ (Thidiazuron), and NAA (1-Naphthylacetic acid), in MS (Murashige and Skoog) nutrient medium were studied. The highest callus proliferation was obtained after 5-week cultivation over a 16-h photoperiod on growth medium MS enriched with 4 muM each of 6-BA and NAA. The medium with 2 muM 6-BA and 4 muM 6-KN had the best shoot induction rate (91.1%) with a mean of 13.4 shoots. The combination of two cytokinins (6-BA and 6-KN) was found to be effective in M. maritima shoot regeneration. The rooting frequency was 100% in 1/2 MS with Indole-3-butyric acid (IBA 2 muM). The number of detected compounds and chemical composition in the M. maritima shoots and seedlings extracts were similar. The total amount of phenolics in the shoots was 216.4% and 369.5% higher than in seedlings and calli, respectively. The total amount of flavonoids in the shoots was 241.1% and 429.3% higher than in seedlings and calli, respectively. The best antioxidant activity was obtained in the shoots, followed by seedlings and calli. However, the order was seedlings > calli > shoots regarding metal chelating ability. The strongest acetylcholinesterase inhibition properties were obtained in the calli, followed by seedlings and shoots. However, the tested samples can be ranked as seedlings > shoots > calli in butylcholinestrase inhibition assay. This study is the first report on the enzyme inhibitory effects of M. maritima extracts, providing valuable contributions to the scientific community.
ESTHER : Song_2020_Plants.(Basel)_9_
PubMedSearch : Song_2020_Plants.(Basel)_9_
PubMedID: 33198181

Title : Phytochemical Composition, Antioxidant Capacity, and Enzyme Inhibitory Activity in Callus, Somaclonal Variant, and Normal Green Shoot Tissues of Catharanthus roseus (L) G. Don - Lee_2020_Molecules_25_4945
Author(s) : Lee ON , Ak G , Zengin G , Cziaky Z , Jeko J , Rengasamy KRR , Park HY , Kim DH , Sivanesan I
Ref : Molecules , 25 :4945 , 2020
Abstract : This study aimed to investigate the impact of plant growth regulators, sucrose concentration, and the number of subcultures on axillary shoot multiplication, in vitro flowering, and somaclonal variation and to assess the phytochemical composition, antioxidant capacity, and enzyme inhibitory potential of in vitro-established callus, somaclonal variant, and normal green shoots of Catharanthus roseus. The highest shoot induction rate (95.8%) and highest number of shoots (23.6), with a mean length of 4.5 cm, were attained when the C. roseus nodal explants (0.6-1 cm in length) were cultivated in Murashige and Skoog (MS) medium with 2 microM thidiazuron, 1 microM 2-(1-naphthyl) acetic acid (NAA), and 4% sucrose. The in vitro flowering of C. roseus was affected by sucrose, and the number of subcultures had a significant effect on shoot multiplication and somaclonal variation. The highest levels of phenolics and flavonoids were found in normal green shoots, followed by those in somaclonal variant shoots and callus. The phytochemicals in C. roseus extracts were qualified using liquid chromatography-tandem mass spectrometry. A total of 39, 55, and 59 compounds were identified in the callus, somaclonal variant shoot, and normal green shoot tissues, respectively. The normal green shoot extracts exhibited the best free radical scavenging ability and reducing power activity. The strongest acetylcholinesterase inhibitory effects were found in the callus, with an IC50 of 0.65 mg/mL.
ESTHER : Lee_2020_Molecules_25_4945
PubMedSearch : Lee_2020_Molecules_25_4945
PubMedID: 33114628

Title : Dracocephalum moldavica attenuates scopolamine-induced cognitive impairment through activation of hippocampal ERK-CREB signaling in mice - Deepa_2020_J.Ethnopharmacol__
Author(s) : Deepa P , Bae HJ , Park HB , Kim SY , Kim S , Choi JW , Kim DH , Liu XQ , Ryu JH , Park SJ
Ref : J Ethnopharmacol , : , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dracocephalum moldavica (Moldavian balm) has been traditionally used for the treatment of intellectual disabilities, migraines and cardiovascular problems in East Asia. Recent scientific studies have demonstrated the usefulness of this plant to treat neurodegenerative disorders, including Alzheimer's disease. AIM OF THE STUDY: This study aimed to investigate the effects of the ethanolic extract of D. moldavica leaves (EEDM) on scopolamine-induced cognitive impairment in mice and the underlying mechanisms of action. MATERIALS AND METHODS: The behavioral effects of EEDM were examined using the step-through passive avoidance and Morris water maze tasks. To elucidate the underlying mechanism, we tested whether EEDM affects acetylcholinesterase activity and the expression of memory-related signaling molecules including extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus. RESULTS: EEDM (25, 50 or 100mg/kg) significantly ameliorated the scopolamine-induced step-through latency reduction in the passive avoidance task in mice. In the Morris water maze task, EEDM (50mg/kg) significantly attenuated scopolamine-induced memory impairment. Furthermore, the administration of EEDM increased the phosphorylation levels of ERK and CREB in the hippocampus but did not alter acetylcholinesterase activity. CONCLUSIONS: These findings suggest that EEDM significantly attenuates scopolamine-induced memory impairment in mice and may be a promising therapeutic agent for improving memory impairment.
ESTHER : Deepa_2020_J.Ethnopharmacol__
PubMedSearch : Deepa_2020_J.Ethnopharmacol__
PubMedID: 32035879

Title : Rapid biodegradation of polyphenylene sulfide plastic beads by Pseudomonas sp - Li_2020_Sci.Total.Environ_720_137616
Author(s) : Li J , Kim HR , Lee HM , Yu HC , Jeon E , Lee S , Kim DH
Ref : Sci Total Environ , 720 :137616 , 2020
Abstract : Pseudomonas sp. isolated from soil, are bioremediating microorganisms that are capable of degrading various types of plastics. Polyphenylene sulfide (PPS) has the most excellent structural stability among general plastics and thus is extremely difficult to break down using physical or chemical methods. This study demonstrates the efficient biodegradation of PPS by Pseudomonas sp., which exists in the gut of superworms. Compared with the conventional film-type of plastic, the degradation efficiencies to the bead form of plastic were significantly improved and thus the biodegradation time was dramatically shortened. Therefore, instead of film-type plastics, we used 300smicrom diameter plastic beads for the measurement of Pseudomonas sp.-mediated biodegradation of PPS during a 10-day period. This method not only can be used for comparison and verification of the biodegradation efficiency of different types of plastics within a short reaction time of 10sdays, but also provides the possibility to develop a new and more efficient screening system to rapidly identify the most efficient species of bacteria for the biodegradation of various types of plastics.
ESTHER : Li_2020_Sci.Total.Environ_720_137616
PubMedSearch : Li_2020_Sci.Total.Environ_720_137616
PubMedID: 32146401

Title : Anti-Obesity Effect of DKB-117 through the Inhibition of Pancreatic Lipase and alpha-Amylase Activity - Kim_2020_Nutrients_12_
Author(s) : Kim DH , Park YH , Lee JS , Jeong HI , Lee KW , Kang TH
Ref : Nutrients , 12 : , 2020
Abstract : This study sought to evaluate the effects of Phaseolus multiflorus var. albus Bailey extract (PM extract) and Pleurotus eryngii var. ferulae extract (PF extract) on the inhibition of digestive enzymes and to confirm the anti-obesity effect of DKB-117 (a mixture of PM extract and PF extract) in digestive enzyme inhibition in a mouse model of obesity induced by a high-fat diet. In in vitro studies, PM extract and PF extract have increased dose-dependent inhibitory activity on alpha-amylase (Inhibitory concentration (IC(50) value: 6.13 mg/mL)) and pancreatic lipase (IC(50) value; 1.68 mg/mL), respectively. High-fat diet-induced obese mice were orally administered DKB-117 extracts at concentrations of 100, 200, and 300 mg/kg/day, while a positive control group was given orlistat (pancreatic lipase inhibitor) and Garcinia cambogia (inhibiting the enzymes needed to synthesize carbohydrates into fat) at concentrations of 40 and 200 mg/kg/day, respectively, for eight weeks. As a result, body weight, fat mass (total fat mass, abdominal fat, and subcutaneous fat) detected with microcomputed tomography, fat mass (abdominal fat and inguinal fat) after an autopsy, and liver triglyceride levels were decreased significantly in the DKB-117 (300 mg/kg/day) group compared to those in the HFD control group. Additionally, we obtained results indicating that the presence of carbohydrates was found more in the DKB-117-300 (300 mg/kg/day) group than in the HFD control group. These data clearly show that DKB-117 extracts are expected to have an anti-obesity effect through a complex mechanism that promotes carbohydrate release through the inhibition of carbohydrate-degrading enzymes while blocking lipid absorption through lipase inhibition.
ESTHER : Kim_2020_Nutrients_12_
PubMedSearch : Kim_2020_Nutrients_12_
PubMedID: 33036193

Title : Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches - Han_2019_Nutrients_11_
Author(s) : Han J , Ji Y , Youn K , Lim G , Lee J , Kim DH , Jun M
Ref : Nutrients , 11 : , 2019
Abstract : One of the major neurodegenerative features of Alzheimer's disease (AD) is the presence of neurotoxic amyloid plaques composed of amyloid beta peptide (Abeta). beta-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Abeta fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), the major efflux pump of the blood-brain barrier (BBB), plays a critical role in limiting therapeutic molecules. In pursuit of discovering a natural anti-AD candidate, the bioactivity, physicochemical, drug-likeness, and molecular docking properties of baicalein, a major compound from Scutellaria baicalensis, was investigated. Baicalein exhibited strong BACE1 and AChE inhibitory properties (IC50 23.71 +/- 1.91 microM and 45.95 +/- 3.44 microM, respectively) and reacted in non-competitive and competitive manners with substrates, respectively. in Silico docking analysis was in full agreement with the in vitro results, demonstrating that the compound exhibited powerful binding interaction with target enzymes. Particularly, three continuous hydroxyl groups on the A ring demonstrated strong H-bond binding properties. It is also noteworthy that baicalein complied with all requirements of Lipinski's rule of five by its optimal physicochemical properties for both oral bioavailability and blood-brain barrier permeability. Overall, the present study strongly demonstrated the possibility of baicalein having in vivo pharmacological efficacy for specific targets in the prevention and/or treatment of AD.
ESTHER : Han_2019_Nutrients_11_
PubMedSearch : Han_2019_Nutrients_11_
PubMedID: 31703329

Title : The effects of pinoresinol on cholinergic dysfunction-induced memory impairments and synaptic plasticity in mice - Yu_2019_Food.Chem.Toxicol_125_376
Author(s) : Yu J , Kwon H , Cho E , Jeon J , Kang RH , Youn K , Jun M , Lee YC , Ryu JH , Kim DH
Ref : Food & Chemical Toxicology , 125 :376 , 2019
Abstract : Dementia is a category of brain diseases that cause a decrease in cognitive functions. Alzheimer's disease (AD) is the most frequently mentioned neurodegenerative disease showing dementia. Although many useful drugs for dementia were developed, we still need better and safer drugs. Here, we tested pinoresinol, a lignan found in sesame seed and olive oil, whether it could be a candidate for this purpose. Pinoresinol (25mg/kg, p.o.) ameliorated memory impairment in dementia model induced by cholinergic blockade in the passive avoidance test in a dose-dependent manner. Moreover, pinoresinol (50muM) facilitated induction of hippocampal long-term potentiation, a cellular model of learning and memory. Pinoresinol blocked acetylcholinesterase (AchE), an acetylcholine-degrading enzyme, activity in a concentration-dependent manner. Moreover, pinoresinol (50muM) facilitated calcium influx into neuro2a cell. These results suggest that pinoresinol improves memory impairment and facilitates hippocampal LTP induction and these results might be related to the effect of pinoresinol on AChE and calcium influx.
ESTHER : Yu_2019_Food.Chem.Toxicol_125_376
PubMedSearch : Yu_2019_Food.Chem.Toxicol_125_376
PubMedID: 30685474

Title : Cognitive-enhancing and ameliorative effects of acanthoside B in a scopolamine-induced amnesic mouse model through regulation of oxidative\/inflammatory\/cholinergic systems and activation of the TrkB\/CREB\/BDNF pathway - Karthivashan_2019_Food.Chem.Toxicol_129_444
Author(s) : Karthivashan G , Kweon MH , Park SY , Kim JS , Kim DH , Ganesan P , Choi DK
Ref : Food & Chemical Toxicology , 129 :444 , 2019
Abstract : Recently, our research team reported the anti-amnesic potential of desalted-hydroethanolic extracts of Salicornia europaea L. (SE-EE). In this study, we performed bioactivity-guided isolation and identification of Acanthoside B (Aca.B), from SE-EE, as the potential bioactive candidate and examined anti-amnesic activity with its potential mechanism of action using an in vivo model. S7-L3-3 purified from SE-EE showed enhanced in vitro acetylcholinesterase (AChE) inhibitory activity. The isolated S7-L3-3 was identified and characterized as Aca.B using varied spectral analyses, i.e., Nuclear magnetic resonance (NMR), Ultraviolet-visible (UV-Vis), and Electrospray ionization-mass spectrometry (ESI-MS). In the in vitro studies, Aca.B exhibited negligible toxicity and showed a dose-dependent nitric oxide inhibitory potential in Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. In the in vivo studies, the oral administration of Aca.B to mice showed enhanced bioavailability and dose-dependent repression of the behavioral/cognitive impairment by regulating the cholinergic function, restoring the antioxidant status, attenuating the inflammatory cytokines/mediators and actively enriching neurotropic proteins in the hippocampal regions of the scopolamine-administered mice.
ESTHER : Karthivashan_2019_Food.Chem.Toxicol_129_444
PubMedSearch : Karthivashan_2019_Food.Chem.Toxicol_129_444
PubMedID: 31077737

Title : Thrombospondin-1 secreted by human umbilical cord blood-derived mesenchymal stem cells rescues neurons from synaptic dysfunction in Alzheimer's disease model - Kim_2018_Sci.Rep_8_354
Author(s) : Kim DH , Lim H , Lee D , Choi SJ , Oh W , Yang YS , Oh JS , Hwang HH , Jeon HB
Ref : Sci Rep , 8 :354 , 2018
Abstract : Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Abeta) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Abeta42-treated mouse hippocampal neurons. Thrombospondin-1 (TSP-1), a protein secreted by hUCB-MSCs in in vitro and 5XFAD AD mouse models, was selected for study. Treatment with exogenous recombinant TSP-1 or co-cultures with hUCB-MSCs significantly increased expression of synaptic-density markers, such as synaptophysin (SYP) and post-synaptic density protein-95 (PSD-95) in Abeta42-treated mouse hippocampal neurons. Knockdown of TSP-1 expression in hUCB-MSCs through small interfering RNA (siRNA) abolished the reversal of Abeta42-induced hippocampal synaptic-density loss. We demonstrate that the rescue effect of hUCB-MSC-secreted TSP-1 was mediated by neuroligin-1 (NLGN1) or alpha2delta-1 receptors. Interestingly, NLGN1 and alpha2delta-1 expression, which was reduced in Abeta42-treated hippocampal neurons, increased in co-cultures with hUCB-MSCs or exogenous TSP-1. Together, these findings suggest that hUCB-MSCs can attenuate Abeta42-induced synaptic dysfunction by regulating TSP-1 release, thus providing a potential alternative therapeutic option for early-stage AD.
ESTHER : Kim_2018_Sci.Rep_8_354
PubMedSearch : Kim_2018_Sci.Rep_8_354
PubMedID: 29321508

Title : Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor - Kwon_2018_Chin.J.Nat.Med_16_428
Author(s) : Kwon H , Jung JW , Lee YC , Ryu JH , Kim DH
Ref : Chin J Nat Med , 16 :428 , 2018
Abstract : Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.
ESTHER : Kwon_2018_Chin.J.Nat.Med_16_428
PubMedSearch : Kwon_2018_Chin.J.Nat.Med_16_428
PubMedID: 30047464

Title : Valorization of onion solid waste and their flavonols for assessment of cytotoxicity, enzyme inhibitory and antioxidant activities - Nile_2018_Food.Chem.Toxicol_119_281
Author(s) : Nile A , Nile SH , Kim DH , Keum YS , Seok PG , Sharma K
Ref : Food & Chemical Toxicology , 119 :281 , 2018
Abstract : Onion (Allium cepa L.) is rich with flavonols which perceived benefits to human health. Flavonols like quercetin and quercetin glycosides from onion solid waste (OSW) have been extracted and tested against enzymes of clinical importance in Alzheimer's disease and diabetes and be shown to have cytotoxic and antioxidant effects. A simple high-performance liquid chromatography-diode array detector method using a Zorbax Eclipse XDB C18 column was developed to separate quercetin-3, 4'-O-diglucoside, quercetin-4'-O-monoglucoside, and quercetin from OSW. These compounds were identified using infrared, ultra-violet, (1)H, and (13)C nuclear magnetic resonance spectroscopic techniques. The OSW solvent fractions and flavonols showed significant antioxidant activities using DPPH (1, 1-diphenyl-2-picrylhydrazyl), FRAP (ferric reducing antioxidant power), and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging assays. The samples exhibited significant in vitro anti-cholinesterase activity with strong antidiabetic effects. OSW extracted with methanol and ethanol showed greater in vitro anti-cholinesterase and hypoglycemic effects than QDG, QMG, and Q possibly due to interactions between multiple compounds and/or complex multivariate interactions with other factors in OSW. In addition, cytotoxicity assays showed that OSW and QDG, QMG, and Q could inhibit the proliferation of selected cancer cell lines. Results indicate that OSW and flavonol glycosides are potential antioxidant, antidiabetic, anticancer, and sedative agents.
ESTHER : Nile_2018_Food.Chem.Toxicol_119_281
PubMedSearch : Nile_2018_Food.Chem.Toxicol_119_281
PubMedID: 29496529

Title : The enhancing effect of Aubang Gahl Soo on the hippocampal synaptic plasticity and memory through enhancing cholinergic system in mice - Lee_2018_J.Ethnopharmacol_224_91
Author(s) : Lee J , Kwon H , Yu J , Cho E , Jeon J , Lee S , Ryu JH , Lee YC , Kim DH , Jung JW
Ref : J Ethnopharmacol , 224 :91 , 2018
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aubang Gahl Soo (AGS) is a Korean traditional drink manufactured from medicinal plants and fruits using sugar or honey. Although traditional old book stated its effects on body, there is no scientific evidence yet. Therefore, in the present study, we tested AGS on brain functions. AIM OF THIS STUDY: In this study, we tried to uncover the effect of on brain functions. To do this we examined the action of AGS on the hippocampal synaptic function and memory in mice. MATERIALS AND METHODS: To examine the effect of AGS on synaptic plasticity, we observed input-output curves (I/O curve), paired-pulse facilitation (PPF), and long-term potentiation (LTP) using mouse hippocampal slices. Moreover, to investigate the functional relevance of the effect of AGS on synaptic plasticity, we conducted passive avoidance, Y-maze and Morris water maze tests. To examine relevant mechanism, acetylcholinesterase (AChE) activity and acetylcholine (ACh) level assay were also conducted. RESULTS: In the basal synaptic transmission study, we found that AGS did not affect I/O curves and PPF. However, AGS facilitated hippocampal LTP in a concentration-dependent manner. Moreover, AGS blocked AChE activity (IC50 = 485mug/ml). Moreover, ACh level was increased by AGS (100mug/ml) treatment. Along with this, facilitating effect of AGS on hippocampal LTP also blocked by scopolamine, a muscarinic acetylcholine receptor antagonist. Moreover, AGS also ameliorated memory impairments induced by scopolamine in passive avoidance, Y-maze, and Morris water maze tests. CONCLUSIONS: These results suggest that AGS facilitates hippocampal LTP through activating cholinergic system and ameliorates cholinergic dysfunction-induced memory deficit.
ESTHER : Lee_2018_J.Ethnopharmacol_224_91
PubMedSearch : Lee_2018_J.Ethnopharmacol_224_91
PubMedID: 29842961

Title : Lactobacillus johnsonii CJLJ103 Attenuates Scopolamine-Induced Memory Impairment in Mice by Increasing BDNF Expression and Inhibiting NF-kappaB Activation - Lee_2018_J.Microbiol.Biotechnol_28_1443
Author(s) : Lee HJ , Lim SM , Kim DH
Ref : J Microbiol Biotechnol , 28 :1443 , 2018
Abstract : In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed TNF-alpha expression and NF-kappaB activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited NF-kappaB activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting NF-kappaB activation.
ESTHER : Lee_2018_J.Microbiol.Biotechnol_28_1443
PubMedSearch : Lee_2018_J.Microbiol.Biotechnol_28_1443
PubMedID: 30111074

Title : The genome of the marine medaka Oryzias melastigma - Kim_2018_Mol.Ecol.Resour_18_656
Author(s) : Kim HS , Lee BY , Han J , Jeong CB , Hwang DS , Lee MC , Kang HM , Kim DH , Lee D , Kim J , Choi IY , Lee JS
Ref : Mol Ecol Resour , 18 :656 , 2018
Abstract : Marine medaka (Oryzias melastigma) is considered to be a useful fish model for marine and estuarine ecotoxicology studies and has good potential for field-based population genomics because of its geographical distribution in Asian estuarine and coastal areas. In this study, we present the first whole-genome draft of O. melastigma. The genome assembly consists of 8,602 scaffolds (N50 = 23.737 Mb) and a total genome length of 779.4 Mb. A total of 23,528 genes were predicted, and 12,670 gene families shared with three teleost species (Japanese medaka, mangrove killifish and zebrafish) were identified. Genome analyses revealed that the O. melastigma genome is highly heterozygous and contains a large number of repeat sequences. This assembly represents a useful genomic resource for fish scientists.
ESTHER : Kim_2018_Mol.Ecol.Resour_18_656
PubMedSearch : Kim_2018_Mol.Ecol.Resour_18_656
PubMedID: 29451363
Gene_locus related to this paper: oryme-a0a3b3dpk3 , oryme-a0a3b3c959 , oryme-a0a3b3d3r3 , oryme-a0a3b3d4c8 , oryme-a0a3b3bnt1 , oryme-a0a3b3caa8 , oryme-a0a3b3bl32 , oryme-a0a3b3da95 , oryme-a0a3b3dps7 , oryme-a0a3b3dej7 , oryme-a0a3b3bpw5 , oryme-a0a3b3c014

Title : Eclalbasaponin II Ameliorates the Cognitive Impairment Induced by Cholinergic Blockade in Mice - Jung_2018_Neurochem.Res_43_351
Author(s) : Jung WY , Kim H , Jeon SJ , Park HJ , Choi HJ , Kim NJ , Kim DH , Jang DS , Ryu JH
Ref : Neurochem Res , 43 :351 , 2018
Abstract : Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3beta (GSK-3beta), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 muM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3beta signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.
ESTHER : Jung_2018_Neurochem.Res_43_351
PubMedSearch : Jung_2018_Neurochem.Res_43_351
PubMedID: 29164430

Title : The ameliorating effect of 1-palmitoyl-2-linoleoyl-3-acetylglycerol on scopolamine-induced memory impairment via acetylcholinesterase inhibition and LTP activation - Jeon_2017_Behav.Brain.Res_324_58
Author(s) : Jeon SJ , Kim B , Park HJ , Zhang J , Kwon Y , Kim DH , Ryu JH
Ref : Behavioural Brain Research , 324 :58 , 2017
Abstract : In the present study, we investigated whether 1-palmitoyl-2-linoleoyl-3-acetylglycerol (PLAG), a component of antlers of Cervus nippon Temminck, would have memory-ameliorating properties against cholinergic blockade-induced memory impairment in mice. In the passive avoidance task to investigate the effects of PLAG on long-term memory, PLAG (10mg/kg, p.o.) administration ameliorated scopolamine-induced memory impairment. PLAG also reversed the impairments of working memory in the Y-maze task and spatial memory as shown in the Morris water maze. To identify the mechanism of the memory-ameliorating effect of PLAG, acetylcholinesterase (AChE) inhibition assay and the Western blot analysis were conducted. In the AChE inhibition assay, PLAG inhibited the AChE activity in mice and PLAG increased the expression levels of phosphorylated CaMKII, ERK, and CREB in the hippocampus. Additionally, long-term potentiation (LTP) of synaptic strength occurred by PLAG treatment in the hippocampal cultures. Overall, the present study suggests that PLAG reversed memory deficits in an animal model and that it affects biochemical pathways related to learning and memory.
ESTHER : Jeon_2017_Behav.Brain.Res_324_58
PubMedSearch : Jeon_2017_Behav.Brain.Res_324_58
PubMedID: 28137622

Title : Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling - Jeon_2017_Neuropharmacol_113_100
Author(s) : Jeon SJ , Lee HJ , Lee HE , Park SJ , Gwon Y , Kim H , Zhang J , Shin CY , Kim DH , Ryu JH
Ref : Neuropharmacology , 113 :100 , 2017
Abstract : Oleanolic acid is a naturally occurring triterpenoid and is widely present in food and medicinal plants. To examine the effect of oleanolic acid on memory deficits, we employed a cholinergic blockade-induced cognitive deficit mouse model. A single administration of oleanolic acid significantly increased the latency on the passive avoidance task and affected the alternation behavior on the Y-maze task and the exploration time on the novel object recognition task, indicating that oleanolic acid reverses the cognitive impairment induced by scopolamine. In accordance with previous reports, oleanolic acid enhanced extracellular-signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Interestingly, ameliorating effect of oleanolic acid on scopolamine-induced memory impairment was abolished by N2-(2-{[(2-oxoazepan-3-yl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide (ANA-12), a potent and specific inhibitor of tropomyosin receptor kinase B (TrkB), in the passive avoidance task. Similarly, oleanolic acid significantly evoked long-term potentiation in a dose-dependent manner, which was diminished by ANA-12 treatment as shown in the electrophysiology study. Together, these results imply that oleanolic acid ameliorates scopolamine-induced memory impairment by modulating the BDNF-ERK1/2-CREB pathway through TrkB activation in mice, suggesting that oleanolic acid would be a potential therapeutic agent for the treatment of cognitive deficits.
ESTHER : Jeon_2017_Neuropharmacol_113_100
PubMedSearch : Jeon_2017_Neuropharmacol_113_100
PubMedID: 27470063

Title : Dankookia rubra gen. nov., sp. nov., an alphaproteobacterium isolated from sediment of a shallow stream - Kim_2016_J.Microbiol_54_420
Author(s) : Kim WH , Kim DH , Kang K , Ahn TY
Ref : J Microbiol , 54 :420 , 2016
Abstract : WS-10(T)-a Gram-negative, non-motile, and aerobic bacterial strain-was isolated from the sediment of a shallow stream in Korea. The optimum ranges of temperature and pH for growth were 20-40 degrees C (optimum 28 degrees C) and pH 6.0-8.0 (optimum pH 7.0), respectively. The DNA G+C content of strain WS-10(T) was 72.7 mol%. The major fatty acids (>5%) were summed feature 8 (C18:1 omega7c), summed feature 3 (C16:1 omega7c and/or C16:1 omega6c), C16:0, and C18:1 2-OH. The major polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, and unidentified aminolipids. Q-10 was the predominant respiratory quinone. The highest similarities in the 16S rRNA gene sequence were shown with Paracraurococcus ruber (95.3%), Belnapia soli (95.3%), B. moabensis (95.1%), and B. rosea (95.0%). A phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that strain WS-10T formed a distinct line within a clade containing the genera Paracraurococcus, Craurococcus, and Belnapia in the family Acetobacteraceae. On the basis of polyphasic evidence, strain WS-10(T) represents a novel species of a new genus in the family Acetobacteraceae, for which the name Dankookia rubra gen. nov., sp. nov. is proposed. The type strain of the type species is WS-10(T) (= KACC 18533(T) = JCM 30602(T)).
ESTHER : Kim_2016_J.Microbiol_54_420
PubMedSearch : Kim_2016_J.Microbiol_54_420
PubMedID: 27225458
Gene_locus related to this paper: 9prot-a0a4r5q8z1

Title : Lactobacillus pentosus var. plantarum C29 increases the protective effect of soybean against scopolamine-induced memory impairment in mice - Yoo_2015_Int.J.Food.Sci.Nutr_66_912
Author(s) : Yoo DH , Kim DH
Ref : Int J Food Sci Nutr , 66 :912 , 2015
Abstract : Biological activities of soybean saponins are dependent on their metabolism by gut microbiota, which generate absorbable bioactive metabolites. Therefore, to enhance the pharmacological effect of soybean, we fermented defatted soybean powder (SP) with Lactobacillus pentosus var. plantarum C29 and measured its protective effect against scopolamine-induced memory impairment in mice using the passive avoidance, Y-maze and Morris water maze tasks. Fermentation increased soyasapogenol B, genistein and daidzein content of soybean and enhanced the protective effect of soybean against scopolamine-induced memory impairment. Additionally, compared with the exthanol extract of soybean, fermented SP (FSP) increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampi of scopolamine-treated mice. Furthermore, FSP inhibited acetylcholinesterase (AChE) activity in vitro and ex vivo. These findings suggest that C29 fermentation might increase the ameliorating effect of soybean against memory impairments by inhibiting AChE activity and increasing BDNF expression.
ESTHER : Yoo_2015_Int.J.Food.Sci.Nutr_66_912
PubMedSearch : Yoo_2015_Int.J.Food.Sci.Nutr_66_912
PubMedID: 26171634

Title : Sphaerotilus natans encrusted with nanoball-shaped Fe(III) oxide minerals formed by nitrate-reducing mixotrophic Fe(II) oxidation - Park_2014_FEMS.Microbiol.Ecol_90_68
Author(s) : Park S , Kim DH , Lee JH , Hur HG
Ref : FEMS Microbiol Ecol , 90 :68 , 2014
Abstract : Ferrous iron has been known to function as an electron source for iron-oxidizing microorganisms in both anoxic and oxic environments. A diversity of bacteria has been known to oxidize both soluble and solid-phase Fe(II) forms coupled to the reduction of nitrate. Here, we show for the first time Fe(II) oxidation by Sphaerotilus natans strain DSM 6575(T) under mixotrophic condition. Sphaerotilus natans has been known to form a sheath structure enclosing long chains of rod-shaped cells, resulting in a thick biofilm formation under oxic conditions. Here, we also demonstrate that strain DSM 6575(T) grows mixotrophically with pyruvate, Fe(II) as electron donors and nitrate as an electron acceptor and single cells of strain DSM 6575(T) are dominant under anoxic conditions. Furthermore, strain DSM 6575(T) forms nanoball-shaped amorphous Fe(III) oxide minerals encrusting on the cell surfaces through the mixotrophic iron oxidation reaction under anoxic conditions. We propose that cell encrustation results from the indirect Fe(II) oxidation by biogenic nitrite during nitrate reduction and that causes the bacterial morphological change to individual rod-shaped single cells from filamentous sheath structures. This study extends the group of existing microorganisms capable of mixotrophic Fe(II) oxidation by a new strain, S. natans strain DSM 6575(T) , and could contribute to biogeochemical cycles of Fe and N in the environment.
ESTHER : Park_2014_FEMS.Microbiol.Ecol_90_68
PubMedSearch : Park_2014_FEMS.Microbiol.Ecol_90_68
PubMedID: 24965827
Gene_locus related to this paper: 9burk-a0a059kik8 , 9burk-a0a059krz1

Title : Soyasaponins Ab and Bb Prevent Scopolamine-Induced Memory Impairment in Mice without the Inhibition of Acetylcholinesterase - Hong_2014_J.Agric.Food.Chem_62_2062
Author(s) : Hong SW , Yoo DH , Woo JY , Jeong JJ , Yang JH , Kim DH
Ref : Journal of Agricultural and Food Chemistry , 62 :2062 , 2014
Abstract : Soy (Glycine max, family Leguminosae), which contains isoflavones and saponins as main constituents, is known to exhibit memory-enhancing effects. Therefore, to investigate the role of soyasaponins in memory impairments, we isolated soyasaponins Ab (SA) and Bb (SB) from soybean and measured their protective effects against scopolamine-induced memory impairment in mice. SA and SB significantly prevented scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Compared to SA, SB rescued memory impairment more potently. Treatment with SB (10 mg/kg, p.o.) protected memory impairment in passive avoidance and Y-maze tasks to 97% (F = 68.10, P < 0.05) and 78% (F = 35.57, P < 0.05) of untreated normal control level, respectively. SA and SB (10 mg/kg) also rescued scopolamine-induced memory impairment in Morris water maze task (F = 14.51, P < 0.05). In addition, soyasaponins preserved brain-derived neurotrophic factor (BNDF) expression (F = 33.69, P < 0.05) and cAMP response element-binding (CREB) protein phosphorylation (F = 91.62, P < 0.05) in the hippocampus of scopolamine-treated mice. However, SA and SB did not inhibit acetylcholinesterase in vitro and ex vivo. On the basis of these findings, we suggest that soybean, particularly soyasaponins, may protect memory impairment by increasing BDNF expression and CREB phosphorylation.
ESTHER : Hong_2014_J.Agric.Food.Chem_62_2062
PubMedSearch : Hong_2014_J.Agric.Food.Chem_62_2062
PubMedID: 24450802

Title : Multiple Cytochrome P450 Isoforms Are Involved in the Generation of a Pharmacologically Active Thiol Metabolite, whereas Paraoxonase 1 and Carboxylesterase 1 Catalyze the Formation of a Thiol Metabolite Isomer from Ticlopidine - Kim_2014_Drug.Metab.Dispos_42_141
Author(s) : Kim MJ , Jeong ES , Park JS , Lee SJ , Ghim JL , Choi CS , Shin JG , Kim DH
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :141 , 2014
Abstract : Ticlopidine is a first-generation thienopyridine antiplatelet drug that prevents adenosine 5'-diphosphate (ADP)-induced platelet aggregation. We identified the enzymes responsible for the two-step metabolic bioactivation of ticlopidine in human liver microsomes and plasma. Formation of 2-oxo-ticlopidine, an intermediate metabolite, was NADPH dependent and cytochrome P450 (CYP) 1A2, 2B6, 2C19, and 2D6 were involved in this reaction. Conversion of 2-oxo-ticlopidine to thiol metabolites was observed in both microsomes (M1 and M2) and plasma (M1). These two metabolites were considered as isomers, and mass spectral analysis suggested that M2 was a thiol metabolite bearing an exocyclic double bond, whereas M1 was an isomer in which the double bond was migrated to an endocyclic position in the piperidine ring. The conversion of 2-oxo-ticlopidine to M1 in plasma was significantly increased by the addition of 1 mM CaCl2. In contrast, the activity in microsomes was not changed in the presence of CaCl2. M1 formation in plasma was inhibited by EDTA but not by other esterase inhibitors, whereas this activity in microsomes was substantially inhibited by carboxylesterase (CES) inhibitors such as bis-(p-nitrophenyl)phosphate (BNPP), diisopropylphosphorofluoride (DFP), and clopidogrel. The conversion of 2-oxo-ticlopidine to M1 was further confirmed with recombinant paraoxonase 1 (PON1) and CES1. However, M2 was detected only in NADPH-dependent microsomal incubation, and multiple CYP isoforms were involved in M2 formation with highest contribution of CYP2B6. In vitro platelet aggregation assay demonstrated that M2 was pharmacologically active. These results collectively indicated that the formation of M2 was mediated by CYP isoforms whereas M1, an isomer of M2, was generated either by human PON1 in plasma or by CES1 in the human liver.
ESTHER : Kim_2014_Drug.Metab.Dispos_42_141
PubMedSearch : Kim_2014_Drug.Metab.Dispos_42_141
PubMedID: 24170778
Gene_locus related to this paper: human-CES1

Title : Angelica keiskei Ameliorates Scopolamine-Induced Memory Impairments in Mice - Oh_2013_Biol.Pharm.Bull_36_82
Author(s) : Oh SR , Kim SJ , Kim DH , Ryu JH , Ahn EM , Jung JW
Ref : Biol Pharm Bull , 36 :82 , 2013
Abstract : Memory impairment is the most common symptom in patients with Alzheimer's disease (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative, analeptic and galactagogue. However, the anti-amnesic effects of AK and its molecular mechanisms have yet to be clearly elucidated. The aim of the present study is to evaluate the effects of AK on scopolamine-induced memory impairments in mice. The regulatory effect of AK on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase (AChE) activity assay was performed to investigate the cholinergic antagonistic effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP response element-binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) were evaluated by Western blot assays and immunohistochemistry. The findings showed that AK significantly attenuated scopolamine-induced cognitive impairment in mice. Increase of AChE activity caused by scopolamine was significantly attenuated by AK. Additionally, AK significantly recovered the phosphorylation of CREB and expression of BDNF reduced by scopolamine in the hippocampus. Taken together, these results provide experimental evidence that AK might be a useful agent in preventing deficit of learning and memory caused by AD and aging.
ESTHER : Oh_2013_Biol.Pharm.Bull_36_82
PubMedSearch : Oh_2013_Biol.Pharm.Bull_36_82
PubMedID: 23132631

Title : The effects of lignan-riched extract of Shisandra chinensis on amyloid-beta-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse - Jeong_2013_J.Ethnopharmacol_146_347
Author(s) : Jeong EJ , Lee HK , Lee KY , Jeon BJ , Kim DH , Park JH , Song JH , Huh J , Lee JH , Sung SH
Ref : J Ethnopharmacol , 146 :347 , 2013
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials. AIM OF STUDY: In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Abeta1-42 injection in mice. MATERIALS AND
METHODS: The fruits of Schisandra chinensis were extracted with the mixture of n-hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Abeta1-42 (2 mug/mouse, i.c.v.), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of beta-secretase and acetylcholinesterase, and the contents of Abeta and the reduced glutathione within the cortex and hippocampus of Abeta-injected mice.
RESULTS: Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Abeta1-42-induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of beta-secretase activity accompanying the reduced level of Abeta1-42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain.
CONCLUSIONS: These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimer's disease.
ESTHER : Jeong_2013_J.Ethnopharmacol_146_347
PubMedSearch : Jeong_2013_J.Ethnopharmacol_146_347
PubMedID: 23333311

Title : Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice - Kim_2013_J.Ethnopharmacol_146_294
Author(s) : Kim EJ , Jung IH , Van Le TK , Jeong JJ , Kim NJ , Kim DH
Ref : J Ethnopharmacol , 146 :294 , 2013
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (family Araliaceae) is traditionally used as a remedy for cancer, inflammation, stress and aging. AIM OF STUDY: To explore whether ginsenosides Rg5 and Rh3, the main constituents of heat-processed ginseng (the root of Panax ginseng), could protect memory deficit. MATERIALS AND
METHODS: We isolated ginsenosides Rh3 and Rg5 from heated-processed ginseng treated with and without human feces, respectively. Then we investigated their protective effects on memory impairment using the passive avoidance, Y-maze and Morris water maze tasks in mice. Memory deficit was induced in mice by the intraperitoneal injection of scopolamine.
RESULTS: Ginsenosides Rg5 or Rh3 increased the latency time reduced by scopolamine in passive avoidance test. Treatment with ginsenoside Rg5 or Rh3 significantly reversed the lowered spontaneous alteration induced by scopolamine in Y-maze task. Ginsenoisde Rg5 or Rh3 (10 mg/kg) significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of training trial sessions in Morris water maze task. Furthermore, ginsenosides Rg5 and Rh3 inhibited acetylcholinesterase activity in a dose-dependent manner, with IC50 values of 18.4 and 10.2 muM, respectively. The inhibitory potency of ginsenoside Rh3 is comparable with that of donepezil (IC50=9.9 muM). These ginsenosides also reversed hippocampal brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation reduced by scopolamine. Of them, ginsenoside Rh3 more potently protected memory deficit.
CONCLUSIONS: Ginsenoside Rg5 and its metabolite ginsenoside Rh3 may protect memory deficit by inhibiting AChE activity and increasing BDNF expression and CREB activation.
ESTHER : Kim_2013_J.Ethnopharmacol_146_294
PubMedSearch : Kim_2013_J.Ethnopharmacol_146_294
PubMedID: 23313392

Title : Aspergillus luchuensis, an industrially important black Aspergillus in East Asia - Hong_2013_PLoS.One_8_e63769
Author(s) : Hong SB , Lee M , Kim DH , Varga J , Frisvad JC , Perrone G , Gomi K , Yamada O , Machida M , Houbraken J , Samson RA
Ref : PLoS ONE , 8 :e63769 , 2013
Abstract : Aspergilli known as black- and white-koji molds which are used for awamori, shochu, makgeolli and other food and beverage fermentations, are reported in the literature as A. luchuensis, A. awamori, A. kawachii, or A. acidus. In order to elucidate the taxonomic position of these species, available ex-type cultures were compared based on morphology and molecular characters. A. luchuensis, A. kawachii and A. acidus showed the same banding patterns in RAPD, and the three species had the same rDNA-ITS, beta-tubulin and calmodulin sequences and these differed from those of the closely related A. niger and A. tubingensis. Morphologically, the three species are not significantly different from each other or from A. niger and A. tubingensis. It is concluded that A. luchuensis, A. kawachii and A. acidus are the same species, and A. luchuensis is selected as the correct name based on priority. Strains of A. awamori which are stored in National Research Institute of Brewing in Japan, represent A. niger (n = 14) and A. luchuensis (n = 6). The neotype of A. awamori (CBS 557.65 = NRRL 4948) does not originate from awamori fermentation and it is shown to be identical with the unknown taxon Aspergillus welwitschiae. Extrolite analysis of strains of A. luchuensis showed that they do not produce mycotoxins and therefore can be considered safe for food and beverage fermentations. A. luchuensis is also frequently isolated from meju and nuruk in Korea and Puerh tea in China and the species is probably common in the fermentation environment of East Asia. A re-description of A. luchuensis is provided because the incomplete data in the original literature.
ESTHER : Hong_2013_PLoS.One_8_e63769
PubMedSearch : Hong_2013_PLoS.One_8_e63769
PubMedID: 23723998
Gene_locus related to this paper: aspaw-AXE1

Title : Cloning and characterization of a novel bifunctional acetyl xylan esterase with carbohydrate binding module from Phanerochaete chrysosporium - Huy_2013_J.Biosci.Bioeng_115_507
Author(s) : Huy ND , Thiyagarajan S , Kim DH , Park SM
Ref : J Biosci Bioeng , 115 :507 , 2013
Abstract : The cDNA of acetyl xylan esterase 2 (PcAxe2) gene containing a carbohydrate binding module (CBM) sequence from Phanerochaete chrysosporium was cloned and expressed in Pichia pastoris. The recombinant PcAxe2 protein (rPcAxe2) was efficiently produced, reaching a maximum of 1058 U l(-1) after 6 days of cultivation. Molecular mass of the rPcAxe2 on SDS-PAGE was approximately 63 kDa under hyperglycosylation. Optimal activity of the purified rPcAxe2 enzyme was observed at pH and temperature of 7.0 and 30-35 degrees C, respectively. In addition to acetyl xylan esterase activity, rPcAxe2 also exhibited a xylanase activity at an optimum pH and temperature of 5.0 and 80 degrees C, respectively. The synergistic action of rPcAxe2 with rPcXynC on birchwood xylan, beechwood xylan and wheat arabinoxylan enhanced the total reducing soluble sugar.
ESTHER : Huy_2013_J.Biosci.Bioeng_115_507
PubMedSearch : Huy_2013_J.Biosci.Bioeng_115_507
PubMedID: 23287498

Title : Lancemaside A isolated from Codonopsis lanceolata and its metabolite echinocystic acid ameliorate scopolamine-induced memory and learning deficits in mice - Jung_2012_Phytomedicine_20_84
Author(s) : Jung IH , Jang SE , Joh EH , Chung J , Han MJ , Kim DH
Ref : Phytomedicine , 20 :84 , 2012
Abstract : The rhizome of Codonopsis lanceolata (family Campanulaceae), which contains lancemaside A as a main constituent, has been used as herbal medicine to treat inflammation, insomnia, and hypomnesia. Lancemaside A and echinocystic acid, which is its metabolite by intestinal microflora, potently inhibited acetylcholinesterase activity in a dose-dependent manner, with IC(50) value 13.6muM and 12.2muM, respectively. Its inhibitory potency is comparable with that of donepezil (IC(50)=10.9muM). Lancemaside A and echinocystic acid significantly reversed scopolamine-induced memory and learning deficits on passive avoidance task. Lancemaside A orally administered 5h before treatment with scopolamine reversed scopolamine-induced memory and learning deficits more potently than one orally administered 1h before. Echinocystic acid more potently reversed it than lancemaside A. Lancemaside A and echinocystic acid significantly reversed scopolamine-induced memory and learning deficits on the Y-maze and Morris water maze tasks. Lancemaside A and echinocystic acid also increased the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (p-CREB). Based on these findings, orally administered lancemaside A may be metabolized to echinocystic acid, which may be absorbed into the blood and ameliorate memory and learning deficits by inhibiting AChE activity and inducing BDNF and p-CREB expressions.
ESTHER : Jung_2012_Phytomedicine_20_84
PubMedSearch : Jung_2012_Phytomedicine_20_84
PubMedID: 23079229

Title : The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Abeta(1-42)-induced cognitive dysfunction in mice - Park_2012_J.Ethnopharmacol_143_611
Author(s) : Park SJ , Jung JM , Lee HE , Lee YW , Kim DH , Kim JM , Hong JG , Lee CH , Jung IH , Cho YB , Jang DS , Ryu JH
Ref : J Ethnopharmacol , 143 :611 , 2012
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid beta(1-42) (Abeta(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Abeta(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain. RESULTS: Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Abeta(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Abeta(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert. CONCLUSION: These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Abeta(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.
ESTHER : Park_2012_J.Ethnopharmacol_143_611
PubMedSearch : Park_2012_J.Ethnopharmacol_143_611
PubMedID: 22846435

Title : Kalopanaxsaponins A and B isolated from Kalopanax pictus ameliorate memory deficits in mice - Joh_2012_Phytother.Res_26_546
Author(s) : Joh EH , Lee IA , Kim DH
Ref : Phytother Res , 26 :546 , 2012
Abstract : The stem-bark of Kalopanax pictus (KP, family Araliaceae), which contains triterpenoid saponins, has been shown to exhibit anticarcinogenic, antiinflammatory, antirheumatoid and antidiabetic activities. In a preliminary study, a KP methanol extract demonstrated acetylcholinesterase activity in vitro and memory enhancement in scopolamine-treated mice. Therefore, we isolated acetylcholinesterase inhibitors, kalopanaxsaponins A and B, from a KP butanol (BuOH) fraction, measured acetylcholinesterase activity in vitro, and investigated their memory-enhancing effects in a passive avoidance test, Y-maze test and Morris water maze test. These constituents inhibited acetylcholinesterase activity and significantly reversed scopolamine-induced deficits. They also increased brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding (p-CREB) protein expression but reduced TNF-alpha increased by scopolamine. Based on these findings, kalopanaxsaponins A and B may ameliorate memory deficits by inhibiting acetylcholinesterase activity and inducing BDNF and p-CREB expression.
ESTHER : Joh_2012_Phytother.Res_26_546
PubMedSearch : Joh_2012_Phytother.Res_26_546
PubMedID: 21928370

Title : The memory-ameliorating effects of Artemisia princeps var. orientalis against cholinergic dysfunction in mice - Liu_2012_Am.J.Chin.Med_40_993
Author(s) : Liu X , Kim DH , Kim JM , Park SJ , Cai M , Jang DS , Ryu JH
Ref : Am J Chin Med , 40 :993 , 2012
Abstract : Artemisia princeps var. orientalis (Compositae) is widely distributed in China, Japan and Korea and is known to have anti-inflammatory and anti-oxidative activities. The ethyl acetate fraction of ethanolic extract of A. princeps var. orientalis (AEA) was found to inhibit acetylcholinesterase activity in a dose-dependent manner in vitro (IC(50) value: 541.4 +/- 67.5 mug/ml). Therefore, we investigated the effects of AEA on scopolamine-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. AEA (100 or 200 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (p < 0.05). In the Morris water maze task, AEA (200 mg/kg, p.o.) significantly shortened escape latencies in training trials and increased both swimming time spent in the target zone and probe crossing numbers during the probe trial as compared with scopolamine-treated mice (p < 0.05). Additionally, the ameliorating effect of AEA on scopolamine-induced memory impairment was antagonized by a subeffective dose of MK-801. These results suggest that AEA could be an effective treatment against cholinergic dysfunction and its effect is mediated by the enhancement of the cholinergic neurotransmitter system via NMDA receptor signaling or acetylcholinesterase inhibition.
ESTHER : Liu_2012_Am.J.Chin.Med_40_993
PubMedSearch : Liu_2012_Am.J.Chin.Med_40_993
PubMedID: 22928830

Title : A novel dipeptidyl peptidase IV inhibitor DA-1229 ameliorates streptozotocin-induced diabetes by increasing beta-cell replication and neogenesis - Cho_2011_Diabetes.Res.Clin.Pract_91_72
Author(s) : Cho JM , Jang HW , Cheon H , Jeong YT , Kim DH , Lim YM , Choi SH , Yang EK , Shin CY , Son MH , Kim SH , Kim HJ , Lee MS
Ref : Diabetes Res Clin Pract , 91 :72 , 2011
Abstract : We studied the effect of a novel dipeptidyl peptidase IV (DPP IV) inhibitor, DA-1229, on blood glucose profile and pancreatic beta-cell mass in established diabetes after streptozotocin (STZ) treatment. Mice that developed diabetes after administration of STZ 100mg/kg were treated with DA-1229 for 13 weeks. DA-1229 significantly reduced plasma DPP IV activity, and enhanced glucagon-like peptide 1 (GLP-1) levels. In STZ-treated mice fed DA-1229 (STZ-DA), blood glucose levels were significantly lower than those in diabetic mice fed normal chow (STZ-NC). Basal and glucose-stimulated insulin secretion and glucose tolerance assessed by intraperitoneal glucose tolerance test were significantly improved by DA-1229 administration. Volume density of beta-cell was significantly increased in STZ-DA mice compared to STZ-NC mice, suggesting that DA-1229-mediated amelioration of established diabetes was due to beneficial effect of DA-1229 on beta-cell mass. The number of replicating beta-cells and that of scattered small beta-cell unit representing beta-cell neogenesis were significantly increased in STZ-DA mice compared to STZ-NC mice, explaining increased beta-cell mass by DA-1229. The expression of PDX-1, a downstream mediator of GLP-1 action, was increased in islets of STZ-DA mice compared to STZ-NC mice. These results suggest a therapeutic potential of DA-1229 in diabetes, particularly that associated with decreased beta-cell mass.
ESTHER : Cho_2011_Diabetes.Res.Clin.Pract_91_72
PubMedSearch : Cho_2011_Diabetes.Res.Clin.Pract_91_72
PubMedID: 21093089

Title : Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice - Lee_2011_Planta.Med_77_1525
Author(s) : Lee IA , Joh EH , Kim DH
Ref : Planta Med , 77 :1525 , 2011
Abstract : The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p. o.) potently reversed scopolamine-induced memory deficits by 62 % and 73 %, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p. o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE.
ESTHER : Lee_2011_Planta.Med_77_1525
PubMedSearch : Lee_2011_Planta.Med_77_1525
PubMedID: 21308615

Title : Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies - Kim_2011_Nucl.Med.Biol_38_541
Author(s) : Kim DH , Choe YS , Choi JY , Lee KH , Kim BT
Ref : Nucl Med Biol , 38 :541 , 2011
Abstract : Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f )-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/mumol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in gamma-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains.
ESTHER : Kim_2011_Nucl.Med.Biol_38_541
PubMedSearch : Kim_2011_Nucl.Med.Biol_38_541
PubMedID: 21531291

Title : Draft genome sequence of Shewanella sp. strain HN-41, which produces arsenic-sulfide nanotubes - Kim_2011_J.Bacteriol_193_5039
Author(s) : Kim DH , Jiang S , Lee JH , Cho YJ , Chun J , Choi SH , Park HS , Hur HG
Ref : Journal of Bacteriology , 193 :5039 , 2011
Abstract : The dissimilatory metal reducing bacterium Shewanella sp. strain HN-41 was first reported to produce novel photoactive As-S nanotubes via reduction of As(V) and S(2)O(3)(2-) under anaerobic conditions. Here we report the draft genome sequence and annotation of strain HN-41.
ESTHER : Kim_2011_J.Bacteriol_193_5039
PubMedSearch : Kim_2011_J.Bacteriol_193_5039
PubMedID: 21868804
Gene_locus related to this paper: 9gamm-f7ru18 , 9gamm-f7rlm5 , 9gamm-f7ris6 , 9gamm-f7rp63

Title : Complete genome sequence of Bifidobacterium longum subsp. longum KACC 91563 - Ham_2011_J.Bacteriol_193_5044
Author(s) : Ham JS , Lee T , Byun MJ , Lee KT , Kim MK , Han GS , Jeong SG , Oh MH , Kim DH , Kim H
Ref : Journal of Bacteriology , 193 :5044 , 2011
Abstract : Bifidobacterium longum strains predominate in the colonic microbiota of breast-fed infants. Here we report the complete genome sequence of B. longum subsp. longum KACC 91563, isolated from feces of neonates. A single circular chromosome of 2,385,301 bp contains 1,980 protein-coding genes, 56 tRNA genes, and 3 rRNA operons.
ESTHER : Ham_2011_J.Bacteriol_193_5044
PubMedSearch : Ham_2011_J.Bacteriol_193_5044
PubMedID: 21742881
Gene_locus related to this paper: bifln-c2gtr2

Title : Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials - Kim_2011_J.Am.Geriatr.Soc_59_1019
Author(s) : Kim DH , Brown RT , Ding EL , Kiel DP , Berry SD
Ref : J Am Geriatr Soc , 59 :1019 , 2011
Abstract : OBJECTIVES: To evaluate the effect of cholinesterase inhibitors (ChEIs) and memantine on the risk of falls, syncope, and related events, defined as fracture and accidental injury. DESIGN: Meta-analysis of randomized controlled trials that were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (no language restriction, through July 2009), and manual search. SETTING: Community and nursing homes. PARTICIPANTS: Participants in fifty-four placebo-controlled randomized trials and extension studies of ChEIs and memantine that reported falls, syncope, and related events in cognitively impaired older adults. MEASUREMENTS: Falls, syncope, fracture, and accidental injury. RESULTS: ChEI use was associated with greater risk of syncope (odds ratio (OR)=1.53, 95% confidence interval (CI)=1.02-2.30) than placebo but not with other events (falls: OR=0.88, 95% CI=0.74-1.04; fracture: OR=1.39, 95% CI=0.75-2.56; accidental injury: OR=1.13, 95% CI=0.87-1.45). Memantine use was associated with fewer fractures (OR=0.21, 95% CI=0.05-0.85) but not with other events (falls: OR=0.92, 95% CI=0.72-1.18; syncope: OR=1.04, 95% CI=0.35-3.04; accidental injury: OR=0.80, 95% CI=0.56-1.12). There was no differential effect according to type and severity of cognitive impairment, residential status, or length of follow-up, although because of underreporting and small number of events, a potential benefit or risk cannot be excluded. CONCLUSION: ChEIs may increase the risk of syncope, with no effects on falls, fracture, or accidental injury in cognitively impaired older adults. Memantine may have a favorable effect on fracture, with no effects on other events. More research is needed to confirm the reduction in fractures observed for memantine.
ESTHER : Kim_2011_J.Am.Geriatr.Soc_59_1019
PubMedSearch : Kim_2011_J.Am.Geriatr.Soc_59_1019
PubMedID: 21649634

Title : Genome sequence of Lactobacillus salivarius NIAS840, isolated from chicken intestine - Ham_2011_J.Bacteriol_193_5551
Author(s) : Ham JS , Kim HW , Seol KH , Jang A , Jeong SG , Oh MH , Kim DH , Kang DK , Kim GB , Cha CJ
Ref : Journal of Bacteriology , 193 :5551 , 2011
Abstract : Lactobacillus salivarius is a well-known lactic acid bacterium to which increasing attention has been paid recently for use as probiotics for humans and animals. L. salivarius NIAS840 was first isolated from broiler chicken feces, displaying antimicrobial activities against multidrug-resistant Staphylococcus aureus and Salmonella enterica serovar Typhimurium. Here, we report the genome sequence of L. salivarius NIAS840 (2,046,557 bp) including a small plasmid and two megaplasmids.
ESTHER : Ham_2011_J.Bacteriol_193_5551
PubMedSearch : Ham_2011_J.Bacteriol_193_5551
PubMedID: 21914873
Gene_locus related to this paper: 9laco-f5vdw9

Title : Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1 - Jung_2010_Life.Sci_87_420
Author(s) : Jung HA , Jin SE , Choi RJ , Kim DH , Kim YS , Ryu JH , Kim DW , Son YK , Park JJ , Choi JS
Ref : Life Sciences , 87 :420 , 2010
Abstract : AIMS: the multifunctional potential of neferine derived from the embryo of Nelumbo nucifera seeds for the age-related neurodegenerative disorders, in vivo anti-amnesic activities and in vitro cholinesterases (ChEs)- and beta-site APP cleaving enzyme 1 (BACE1)-inhibitory activities, as well as anti-inflammatory and antioxidant activities were investigated. MAIN METHODS: in vivo anti-amnesic activities were performed via the passive avoidance, Y-maze, and Morris water maze tasks in a scopolamine-induced amnesia model. The cell-free antioxidant capacities were evaluated by in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals, and peroxynitrite (ONOO(-)), as well as inhibitory activities against nitric oxide (NO), superoxide anion (O(2)(-)), lipid peroxidation, and ONOO(-)-mediated tyrosine nitration. The intracellular antioxidant capacities were also determined via inhibitory activities of lipopolysaccharide (LPS)-induced NO generation and NF-kappaB activation in RAW 264.7 cells. KEY FINDINGS: neferine showed significant improvement in cognitive impairment in scopolamine-induced amnesia animal models and moderate inhibitory activities in ChEs and BACE1 assays. In addition, it exhibited notable scavenging activities against DPPH, ABTS, NO, and O(2)(-) radicals, as well as ONOO(-). Neferine also demonstrated remarkable inhibitory activity against lipid peroxidation and protein nitration in cell-free antioxidant assays and moderate inhibitory activity of NO generation with exceptional suppression of NF-kappaB activation in cell-based assays. SIGNIFICANCE: the results demonstrate that the anti-amnesic effect of neferine may be mediated via antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1.
ESTHER : Jung_2010_Life.Sci_87_420
PubMedSearch : Jung_2010_Life.Sci_87_420
PubMedID: 20736023

Title : Anti-amnesic effect of ESP-102 on Abeta(1-42)-induced memory impairment in mice - Kim_2010_Pharmacol.Biochem.Behav_97_239
Author(s) : Kim DH , Jung WY , Park SJ , Kim JM , Lee S , Kim YC , Ryu JH
Ref : Pharmacol Biochem Behav , 97 :239 , 2010
Abstract : The aim of this study was to characterize the effects of ESP-102 on the memory impairments and pathological changes induced by amyloid-beta (Abeta)(1-42) peptide in mice. The ameliorating effect of ESP-102 on memory impairment was investigated using the passive avoidance and the Morris water maze tasks, and the pathological changes were identified by immunohistochemistry and western blotting. Abeta(1-42) peptide (3mug/3mul) was administered by intracerebroventricular injection. By the single administration of ESP-102 (100mg/kg, p.o), the memory impairment induced by Abeta(1-42) peptide was significantly attenuated (P<0.05). Moreover, ESP-102 (100mg/kg, p.o) significantly inhibited acetylcholinesterase (AChE) activity in the hippocampus compared to the Abeta(1-42) peptide-injected control group. In the subchronic treatment study, ESP-102 (50 or 100mg/kg/day, p.o) administration for seven days ameliorated the memory impairments induced by Abeta(1-42) peptide. Moreover, ESP-102 inhibited lipid peroxidation induced by Abeta(1-42) peptide in the hippocampus. Abeta(1-42)-induced increases in the expression of GFAP (an astrocyte marker) and inducible nitric oxide synthase (iNOS) in the hippocampal region were also attenuated by ESP-102 treatment. These results suggest that the ameliorating effect of ESP-102 on Abeta(1-42) peptide-induced memory impairment is mediated via its AChE inhibitory, antioxidative, and/or anti-inflammatory activities.
ESTHER : Kim_2010_Pharmacol.Biochem.Behav_97_239
PubMedSearch : Kim_2010_Pharmacol.Biochem.Behav_97_239
PubMedID: 20728465

Title : Mangiferin ameliorates scopolamine-induced learning deficits in mice - Jung_2009_Biol.Pharm.Bull_32_242
Author(s) : Jung K , Lee B , Han SJ , Ryu JH , Kim DH
Ref : Biol Pharm Bull , 32 :242 , 2009
Abstract : The aim of this study was to evaluate the effects of Anemarrhena asphodeloides BUNGE (AA) on cholinergic memory deficits in mice. This agent has previously been used as an antipyretic, anti-inflammatory, anti-diabetic, and antidepressant in traditional Chinese medicine. Mangiferin was isolated from AA and showed a dose-dependent inhibition of acetylcholinesterase (AChE) activity (IC(50) value, 62.8 microM). Cholinergic dysfunction was induced in mice by administering scopolamine, and the animals were then tested using the passive avoidance test as well as the Morris water maze test. Mangiferin (20 mg/kg, p.o.) significantly reversed scopolamine-induced deficits in the passive avoidance test, and also improved escape latencies in training trials and increased swimming times in the Morris water maze test (p<0.05). Mangiferin also reduced acetylcholine and tumor necrosis factor (TNF)-alpha levels induced by scopolamine in mice brain (p<0.05) and inhibited nuclear factor (NF)-kappaB activation in scopolamine or TNF-alpha-stimulated BV-2 microglial cells. These results suggest that mangiferin can improve long-term cholinergic memory deficits by AChE inhibition or cholinergic receptor stimulation and inhibition of NF-kappaB activation.
ESTHER : Jung_2009_Biol.Pharm.Bull_32_242
PubMedSearch : Jung_2009_Biol.Pharm.Bull_32_242
PubMedID: 19182383

Title : Gluco-obtusifolin and its aglycon, obtusifolin, attenuate scopolamine-induced memory impairment - Kim_2009_J.Pharmacol.Sci_111_110
Author(s) : Kim DH , Hyun SK , Yoon BH , Seo JH , Lee KT , Cheong JH , Jung SY , Jin C , Choi JS , Ryu JH
Ref : J Pharmacol Sci , 111 :110 , 2009
Abstract : In the present study, we assessed the effects of gluco-obtusifolin, isolated from the seeds of Cassia obtusifolia L., and its aglycone, obtusifolin, on the learning and memory impairments induced by scopolamine using the passive avoidance and the Morris water maze tasks in mice. Gluco-obtusifolin (1, 2, and 4 mg/kg, p.o.) and obtusifolin (0.25, 0.5, 1, and 2 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test (P<0.05). Moreover, gluco-obtusifolin (2 mg/kg, p.o.) and obtusifolin (0.5 mg/kg, p.o.) improved escape latencies, swimming times in the target quadrant, and crossing numbers in the zone where the platform previously existed in the Morris water maze test. In the acetylcholinesterase assay, gluco-obtusifolin and obtusifolin were found to inhibit acetylcholinesterase activity in vitro (IC(50) = 37.2 and 18.5 microM, respectively) and ex vivo. These results suggest that gluco-obtusifolin and its aglycone may be useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, by the enhancement of cholinergic signaling.
ESTHER : Kim_2009_J.Pharmacol.Sci_111_110
PubMedSearch : Kim_2009_J.Pharmacol.Sci_111_110
PubMedID: 19834282

Title : Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice - Lee_2009_Pharmacol.Biochem.Behav_93_121
Author(s) : Lee B , Jung K , Kim DH
Ref : Pharmacol Biochem Behav , 93 :121 , 2009
Abstract : Anemarrhena asphodeloides Bunge (AA, family Liliaceae), which primarily contains xantones, such as mangiferin, and steroidal saponins, such as timosaponin AIII and sarsasapogenin, has been used as an anti-pyretic, anti-inflammatory, anti-diabetic, anti-platelet aggregation, and anti-depressant agent in traditional Chinese medicine. In the present study, the memory-enhancing effects of these saponins were investigated in scopolamine-treated mice. Among saponins, timosaponin AIII (TA3) significantly reversed the scopolamine-induced deficits in a passive avoidance test and in the Morris water maze test. TA3 also increased hippocampal acetylcholine levels in scopolamine-treated mice and dose-dependently inhibited acetylcholinesterase (AChE) activity (IC(50) value, 35.4 microM). When TA3 (50 mg/kg) was orally administered to mice and its blood concentration was measured by liquid chromatography and tandem mass spectrometry, the C(max) of TA3 occurred 4-6 h after TA3 treatment. The memory-enhancing effect of TA3 was greater when it was administered 5 h before the acquisition trial than 1 h before. Scopolamine treatment in mice increased brain levels of TNF-alpha and IL-1beta expression. However, treatment with TA3 and scopolamine inhibited the increase of TNF-alpha and IL-1beta expression. These results suggest that scopolamine may cause learning and memory deficits that are further complicated by inflammation. TA3 also inhibited the activation of NF-kappaB signaling in BV-2 microglia and in SK-N-SH neuroblastoma cells induced with TNF-alpha or scopolamine. Nevertheless, TA3 may ameliorate memory deficits, mainly by inhibiting AChE.
ESTHER : Lee_2009_Pharmacol.Biochem.Behav_93_121
PubMedSearch : Lee_2009_Pharmacol.Biochem.Behav_93_121
PubMedID: 19426756

Title : Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice - Kim_2007_Life.Sci_80_1944
Author(s) : Kim DH , Kim DY , Kim YC , Jung JW , Lee S , Yoon BH , Cheong JH , Kim YS , Kang SS , Ko KH , Ryu JH
Ref : Life Sciences , 80 :1944 , 2007
Abstract : Nodakenin is a coumarin compound initially isolated from the roots of Angelica gigas. In the present study, we investigated the effects of nodakenin on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) using the passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Nodakenin (10 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in the passive avoidance test and the Y-maze test (P<0.05), and also reduced escape latency during training in the Morris water maze test (P<0.05). Moreover, swimming times and distances within the target zone of the Morris water maze were greater in the nodakenin-treated group than in the scopolamine-treated group (P<0.05). In an in vitro study, nodakenin was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50)=84.7 microM). In addition, nodakenin was also found to inhibit acetylcholinesterase activity for 6 h in an ex-vivo study. These results suggest that nodakenin may be a useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, via the enhancement of cholinergic signaling.
ESTHER : Kim_2007_Life.Sci_80_1944
PubMedSearch : Kim_2007_Life.Sci_80_1944
PubMedID: 17382968

Title : The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice - Kim_2007_J.Pharmacol.Sci_105_82
Author(s) : Kim DH , Yoon BH , Kim YW , Lee S , Shin BY , Jung JW , Kim HJ , Lee YS , Choi JS , Kim SY , Lee KT , Ryu JH
Ref : J Pharmacol Sci , 105 :82 , 2007
Abstract : In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.
ESTHER : Kim_2007_J.Pharmacol.Sci_105_82
PubMedSearch : Kim_2007_J.Pharmacol.Sci_105_82
PubMedID: 17895591

Title : Gomisin A improves scopolamine-induced memory impairment in mice - Kim_2006_Eur.J.Pharmacol_542_129
Author(s) : Kim DH , Hung TM , Bae KH , Jung JW , Lee S , Yoon BH , Cheong JH , Ko KH , Ryu JH
Ref : European Journal of Pharmacology , 542 :129 , 2006
Abstract : Gomisin A is a component of the fruits of Schizandra chinesis which are widely used as a tonic in traditional Chinese medicine. In the present study, we assessed the effect of gomisin A on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of gomisin A was investigated using a passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Gomisin A (5 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in mice by the passive avoidance test and the Y-maze test (P<0.05), and also improved escape latency in the Morris water maze test at 5 mg/kg (P<0.05). Moreover, in an in vitro study, gomisin A was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC50 value; 15.5 microM). These results suggest that gomisin A may be a useful cognitive impairment treatment, and its beneficial effects are mediated, in part, via enhancing the cholinergic nervous system.
ESTHER : Kim_2006_Eur.J.Pharmacol_542_129
PubMedSearch : Kim_2006_Eur.J.Pharmacol_542_129
PubMedID: 16824513

Title : The genomic sequence of the accidental pathogen Legionella pneumophila - Chien_2004_Science_305_1966
Author(s) : Chien M , Morozova I , Shi S , Sheng H , Chen J , Gomez SM , Asamani G , Hill K , Nuara J , Feder M , Rineer J , Greenberg JJ , Steshenko V , Park SH , Zhao B , Teplitskaya E , Edwards JR , Pampou S , Georghiou A , Chou IC , Iannuccilli W , Ulz ME , Kim DH , Geringer-Sameth A , Goldsberry C , Morozov P , Fischer SG , Segal G , Qu X , Rzhetsky A , Zhang P , Cayanis E , de Jong PJ , Ju J , Kalachikov S , Shuman HA , Russo JJ
Ref : Science , 305 :1966 , 2004
Abstract : We present the genomic sequence of Legionella pneumophila, the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45-kilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets.
ESTHER : Chien_2004_Science_305_1966
PubMedSearch : Chien_2004_Science_305_1966
PubMedID: 15448271
Gene_locus related to this paper: legph-q5zsu4 , legpa-q5x2r4 , legpa-q5x3a5 , legpa-q5x3d6 , legpa-q5x4r4 , legpa-q5x4t1 , legpa-q5x5b2 , legpa-q5x5z2 , legpa-q5x7f5 , legpa-q5x8e6 , legpa-q5x8m4 , legpa-q5x322 , legpa-q5x405 , legpa-q5x424 , legpa-q5x473 , legpa-q5x590 , legpa-q5x611 , legpa-q5x819 , legpc-a5iar0 , legph-q5zrh1 , legph-q5zsb5 , legph-q5zv00 , legph-q5zwi8 , legph-q5zze3 , legpl-q5wtd3 , legpl-q5wua5 , legpl-q5wvw9 , legpn-Q8KU34 , legpn-Q8RNQ1 , legpn-SBPA , legpn-i7i328 , legpl-q5wsw9

Title : A simple and efficient in vitro method for metabolism studies of radiotracers - Lee_2001_Nucl.Med.Biol_28_391
Author(s) : Lee SY , Choe YS , Kim DH , Park BN , Kim SE , Choi Y , Lee KH , Lee J , Kim BT
Ref : Nucl Med Biol , 28 :391 , 2001
Abstract : In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.
ESTHER : Lee_2001_Nucl.Med.Biol_28_391
PubMedSearch : Lee_2001_Nucl.Med.Biol_28_391
PubMedID: 11395311

Title : Oxo-type organophosphate-resistant acetylcholinesterase from organophosphate-unsusceptible Culex tritaeniorhynchus -
Author(s) : Watanabe M , Takebe S , Kim DH , Arakawa R , Kamimura K , Kobashi K
Ref : Chem Pharm Bull (Tokyo) , 36 :312 , 1988
PubMedID: 3378294